Escitalopram reduces attentional performance in anxious older adults with high-expression genetic variants at serotonin 2A and 1B receptors

Older adults are among the most vulnerable to adverse cognitive effects of psychotropic medications and, therefore, the personalization of psychotropic treatment based on adverse drug reactions in this demographic is of great importance. We examined changes on neuropsychological tests of attention attributable to selective serotonin reuptake inhibitor (SSRI) treatment in anxious older adults. We also examined whether variation in serotonin receptor genes was associated with reduced attentional performance with SSRIs. We examined change from pre- to post-treatment in two attention measures – digit span and coding – in 133 adults aged ≥60 yr with generalized anxiety disorder in a 12-wk trial of escitalopram vs. placebo. We also examined attentional change in relation to genetic variability in four central serotonin receptors: the serotonin transporter and serotonin 1A, 2A and 1B receptors. Digit span scores were significantly lowered in patients receiving escitalopram relative to placebo, indicating reduced attentional performance attributable to the SSRI. Individuals with high-transcription variants in the receptors 5-HTR(2A) rs6311 and 5-HTR(1B) rs11568817 had greater reductions in attention with SSRI treatment compared to placebo. We conclude that SSRIs reduce attention in older adults, particularly in those with high-expression genetic variants at the serotonin 2A and 1B receptors. Analysing neuropsychological changes with SSRIs in relation to genetic variation in the serotonin system may be a useful strategy for detecting subgroups of older adults who are more susceptible to side-effects of SSRIs. These results, if confirmed, could lead to the personalization of SSRI use to reduce adverse neurocognitive effects

Unravelling controls on multi-source-to-sink systems:A stratigraphic forward model of the early–middle Cenozoic of the SW Barents Sea

Source-to-sink dynamics are subjected to complex interactions between erosion, sediment transfer and deposition, particularly in an evolving tectonic and climatic setting. Here we use stratigraphic forward modelling (SFM) to predict the basin-fill architecture of a multi-source-to-sink system based on a state-of-the-art numerical approach. The modelling processes consider key source-to-sink parameters such as water discharge, sediment load and grain size to simulate various sedimentary processes and transport mechanisms reflecting the dynamic interplay between erosion in the catchment area, subsidence, deposition and filling of the basin. The Cenozoic succession along the SW Barents Shelf margin provides a key area to examine controls on source-to-sink systems along a transform margin that developed during the opening of the North Atlantic when Greenland and Eurasian plates were separated (ca. 55 Ma onwards). Moreover, the gradual cooling which culminated in major glaciations in the northern hemisphere during the Quaternary (ca. 2.7 Ma), has affected the spatio-temporal evolution of the sediment routing along the western Barents Shelf margin. This study aims to characterize the relative importance of different source areas within the source-to-sink framework through SFM. In the early Eocene, the SW Barents Shelf experienced a relatively equal sediment delivery from three principal source areas: (i) Greenland to the north, (ii) the Stappen High to the east, representing a local source terrain, and (iii) a major southern source (Fennoscandia). In the middle Eocene, our best-fit modelling scenario suggests that the northern and the local eastern sources dominated over the southern source, collectively supplying large amounts of sand into the basin as evidenced by the submarine fans in Sørvestsnaget Basin. In the Oligocene (ca. 33 Ma) and Miocene (ca. 23 Ma), significant amounts of sediments were sourced from the east due to shelf-wide uplift. Finally, this study highlights the dynamic nature and controls of sediment transfer in multi-source-to-sink systems and demonstrates the potential of SFM to unravel tectonic and climatic signals in the stratigraphic record

Pointing control for the SPIDER balloon-borne telescope

We present the technology and control methods developed for the pointing system of the SPIDER experiment. SPIDER is a balloon-borne polarimeter designed to detect the imprint of primordial gravitational waves in the polarization of the Cosmic Microwave Background radiation. We describe the two main components of the telescope's azimuth drive: the reaction wheel and the motorized pivot. A 13 kHz PI control loop runs on a digital signal processor, with feedback from fibre optic rate gyroscopes. This system can control azimuthal speed with < 0.02 deg/s RMS error. To control elevation, SPIDER uses stepper-motor-driven linear actuators to rotate the cryostat, which houses the optical instruments, relative to the outer frame. With the velocity in each axis controlled in this way, higher-level control loops on the onboard flight computers can implement the pointing and scanning observation modes required for the experiment. We have accomplished the non-trivial task of scanning a 5000 lb payload sinusoidally in azimuth at a peak acceleration of 0.8 deg/s$^2$, and a peak speed of 6 deg/s. We can do so while reliably achieving sub-arcminute pointing control accuracy.Comment: 20 pages, 12 figures, Presented at SPIE Ground-based and Airborne Telescopes V, June 23, 2014. To be published in Proceedings of SPIE Volume 914

Planck intermediate results: XVI. Profile likelihoods for cosmological parameters

We explore the 2013 Planck likelihood function with a high-precision multi-dimensional minimizer (Minuit). This allows a refinement of the ΛCDM best-fit solution with respect to previously-released results, and the construction of frequentist confidence intervals using profile likelihoods. The agreement with the cosmological results from the Bayesian framework is excellent, demonstrating the robustness of the Planck results to the statistical methodology. We investigate the inclusion of neutrino masses, where more significant differences may appear due to the non-Gaussian nature of the posterior mass distribution. By applying the Feldman-Cousins prescription, we again obtain results very similar to those of the Bayesian methodology. However, the profile-likelihood analysis of the cosmic microwave background (CMB) combination (Planck+WP+highL) reveals a minimum well within the unphysical negative-mass region. We show that inclusion of the Planck CMB-lensing information regularizes this issue, and provide a robust frequentist upper limit ∑ mν ≤ 0.26 eV (95% confidence) from the CMB+lensing+BAO data combination. Reproduced with permission from Astronomy & Astrophysics, © ESO 201

L. Evidence of spatial variation of the polarized thermal dust spectral energy distribution and implications for CMB B-mode analysis

Planck Collaboration.The characterization of the Galactic foregrounds has been shown to be the main obstacle in thechallenging quest to detect primordial B-modes in the polarized microwave sky. We make use of the Planck-HFI 2015 data release at high frequencies to place new constraints on the properties of the polarized thermal dust emission at high Galactic latitudes. Here, we specifically study the spatial variability of the dust polarized spectral energy distribution (SED), and its potential impact on the determination of the tensor-to-scalar ratio, r. We use the correlation ratio of the angular power spectra between the 217 and 353 GHz channels as a tracer of these potential variations, computed on different high Galactic latitude regions, ranging from 80% to 20% of the sky. The new insight from Planck data is a departure of the correlation ratio from unity that cannot be attributed to a spurious decorrelation due to the cosmic microwave background, instrumental noise, or instrumental systematics. The effect is marginally detected on each region, but the statistical combination of all the regions gives more than 99% confidence for this variation in polarized dust properties. In addition, we show that the decorrelation increases when there is a decrease in the mean column density of the region of the sky being considered, and we propose a simple power-law empirical model for this dependence, which matches what is seen in the Planck data. We explore the effect that this measured decorrelation has on simulations of the BICEP2-Keck Array/Planck analysis and show that the 2015 constraints from these data still allow a decorrelation between the dust at 150 and 353 GHz that is compatible with our measured value. Finally, using simplified models, we show that either spatial variation of the dust SED or of the dust polarization angle are able to produce decorrelations between 217 and 353 GHz data similar to the values we observe in the data.The Planck Collaboration acknowledges the support of: ESA; CNES, and CNRS/INSU-IN2P3-INP (France); ASI, CNR, and INAF (Italy); NASA and DoE (USA); STFC and UKSA (UK); CSIC, MINECO, J.A., and RES (Spain); Tekes, AoF, and CSC (Finland); DLR and MPG (Germany); CSA (Canada); DTU Space (Denmark); SER/SSO (Switzerland); RCN (Norway); SFI (Ireland); FCT/MCTES (Portugal); ERC and PRACE (EU). The research leading to these results has received funding from the European Research Council under the European Union’s Seventh Framework Programme (FP7/2007-2013) / ERC grant agreement No. 267934.Peer Reviewe

Planck intermediate results. XIX. An overview of the polarized thermal emission from Galactic dust

This paper presents an overview of the polarized sky as seen by Planck HFI at 353 GHz, which is the most sensitive Planck channel for dust polarization. We construct and analyse maps of dust polarization fraction and polarization angle at 1° resolution, taking into account noise bias and possible systematic effects. The sensitivity of the Planck HFI polarization measurements allows for the first time a mapping of Galactic dust polarized emission on large scales, including low column density regions. We find that the maximum observed dust polarization fraction is high (pmax = 19.8%), in particular in some regions of moderate hydrogen column density (NH < 2 × 1021 cm-2). The polarization fraction displays a large scatter at NH below a few 1021 cm-2. There is a general decrease in the dust polarization fraction with increasing column density above NH ≃ 1 × 1021 cm-2 and in particular a sharp drop above NH ≃ 1.5 × 1022 cm-2. We characterize the spatial structure of the polarization angle using the angle dispersion function. We find that the polarization angle is ordered over extended areas of several square degrees, separated by filamentary structures of high angle dispersion function. These appear as interfaces where the sky projection of the magnetic field changes abruptly without variations in the column density. The polarization fraction is found to be anti-correlated with the dispersion of polarization angles. These results suggest that, at the resolution of 1°, depolarization is due mainly to fluctuations in the magnetic field orientation along the line of sight, rather than to the loss of grain alignment in shielded regions. We also compare the polarization of thermal dust emission with that of synchrotron measured with Planck, low-frequency radio data, and Faraday rotation measurements toward extragalactic sources. These components bear resemblance along the Galactic plane and in some regions such as the Fan and North Polar Spur regions. The poor match observed in other regions shows, however, that dust, cosmic-ray electrons, and thermal electrons generally sample different parts of the line of sight. Reproduced with permission, © ESO, 201

Haptoglobin Treatment for Aneurysmal Subarachnoid Hemorrhage: Review and Expert Consensus on Clinical Translation

Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating form of stroke frequently affecting young to middle-aged adults, with an unmet need to improve outcome. This special report focusses on the development of intrathecal haptoglobin supplementation as a treatment by reviewing current knowledge and progress, arriving at a Delphi-based global consensus regarding the pathophysiological role of extracellular hemoglobin and research priorities for clinical translation of hemoglobin-scavenging therapeutics. After aneurysmal subarachnoid hemorrhage, erythrocyte lysis generates cell-free hemoglobin in the cerebrospinal fluid, which is a strong determinant of secondary brain injury and long-term clinical outcome. Haptoglobin is the body's first-line defense against cell-free hemoglobin by binding it irreversibly, preventing translocation of hemoglobin into the brain parenchyma and nitric oxide-sensitive functional compartments of cerebral arteries. In mouse and sheep models, intraventricular administration of haptoglobin reversed hemoglobin-induced clinical, histological, and biochemical features of human aneurysmal subarachnoid hemorrhage. Clinical translation of this strategy imposes unique challenges set by the novel mode of action and the anticipated need for intrathecal drug administration, necessitating early input from stakeholders. Practising clinicians (n=72) and scientific experts (n=28) from 5 continents participated in the Delphi study. Inflammation, microvascular spasm, initial intracranial pressure increase, and disruption of nitric oxide signaling were deemed the most important pathophysiological pathways determining outcome. Cell-free hemoglobin was thought to play an important role mostly in pathways related to iron toxicity, oxidative stress, nitric oxide, and inflammation. While useful, there was consensus that further preclinical work was not a priority, with most believing the field was ready for an early phase trial. The highest research priorities were related to confirming haptoglobin's anticipated safety, individualized versus standard dosing, timing of treatment, pharmacokinetics, pharmacodynamics, and outcome measure selection. These results highlight the need for early phase trials of intracranial haptoglobin for aneurysmal subarachnoid hemorrhage, and the value of early input from clinical disciplines on a global scale during the early stages of clinical translation

Planck intermediate results. XV. A study of anomalous microwave emission in Galactic clouds

Anomalous microwave emission (AME) is believed to be due to electric dipole radiation from small spinning dust grains. The aim of this paper is a statistical study of the basic properties of AME regions and the environment in which they emit. We used WMAP and Planck maps, combined with ancillary radio and IR data, to construct a sample of 98 candidate AME sources, assembling SEDs for each source using aperture photometry on 1°-smoothed maps from 0.408 GHz up to 3000 GHz. Each spectrum is fitted with a simple model of free-free, synchrotron (where necessary), cosmic microwave background (CMB), thermal dust, and spinning dust components. We find that 42 of the 98 sources have significant (>5σ) excess emission at frequencies between 20 and 60 GHz. An analysis of the potential contribution of optically thick free-free emission from ultra-compact H ii regions, using IR colour criteria, reduces the significant AME sample to 27 regions. The spectrum of the AME is consistent with model spectra of spinning dust. Peak frequencies are in the range 20−35 GHz except for the California nebula (NGC 1499), which appears to have a high spinning dust peak frequency of (50 ± 17) GHz. The AME regions tend to be more spatially extended than regions with little or no AME. The AME intensity is strongly correlated with the sub-millimetre/IR flux densities and comparable to previous AME detections in the literature. AME emissivity, defined as the ratio of AME to dust optical depth, varies by an order of magnitude for the AME regions. The AME regions tend to be associated with cooler dust in the range 14−20 K and an average emissivity index, βd, of +1.8, while the non-AME regions are typically warmer, at 20−27 K. In agreement with previous studies, the AME emissivity appears to decrease with increasing column density. This supports the idea of AME originating from small grains that are known to be depleted in dense regions, probably due to coagulation onto larger grains. We also find a correlation between the AME emissivity (and to a lesser degree the spinning dust peak frequency) and the intensity of the interstellar radiation field, G0. Modelling of this trend suggests that both radiative and collisional excitation are important for the spinning dust emission. The most significant AME regions tend to have relatively less ionized gas (free-free emission), although this could be a selection effect. The infrared excess, a measure of the heating of dust associated with H ii regions, is typically >4 for AME sources, indicating that the dust is not primarily heated by hot OB stars. The AME regions are associated with known dark nebulae and have higher 12 μm/25 μm ratios. The emerging picture is that the bulk of the AME is coming from the polycyclic aromatic hydrocarbons and small dust grains from the colder neutral interstellar medium phase. Reproduced with permission from Astronomy & Astrophysics, © ESO 201